This is one of those stories with the potential to shift billions of dollars in pharmaceutical sales from one class of drugs to another, so we should all understand that there may be more than science motivating the conclusion. However, it has been widely reported in the press and deserves discussion in this blog.

Depression is widely diagnosed in the USA. It is also commonly treated with a class of anti-depressant drugs known as SSRI's (selective serotonin reuptake inhibitors). Now, research from the Fisher Center for Alzheimer's Disease at the Rockefeller University suggests that the effects of these drugs can be largely negated by common pain killers such as aspirin, ibuprofen, and naproxen.

The most common SSRI's are well known by their brand names, Zoloft, Prozac, and Paxil, and they constitute the most widely prescribed class of drugs in this country. Millions of people spend millions of dollars annually to treat depression. However, since pain medications are also commonly consumed, this research suggests a massive potential treatment conundrum.

I think it is fair to suggest that there may be a relationship between the efficacy of SSRI's and over-the-counter pain medications. But it is also fair to recognize that this is merely a suggestive finding at this point, with no peer-reviewed publication describing the conclusion as yet.

If a publication follows, and others duplicate the findings, this could become a very big story. For now, it is a point of interest, and something to discuss with your physician if you feel your anti-depressant is ineffective.

Stem cell research has a controversial past, a murky present, and a bright future.

While there has been heated debate about the ethics of harvesting stem cells for research, all but the most ardent critics seem to be acceptig that there are morally sound approaches to such work. Furthermore, a strong case can be made that, to ignore the great promise of life changing benefits that stem cell research might yield, would give rise to equally profound moral questions.

A great overview of the issue, and how stem cell research is marching steadily toward better treatments for Alzheimer's disease was published last week by Northwestern University. In a Q&A session with Dr. John Kessler, this article succinctly explains his work, the current challenges, and the bright future of stem cell-based therapy for a host of daunting medical conditions.

A few days ago, I wrote about some "negative press" for the Alzheimer's drug Namenda, that I felt was misleading. Basically, it was a series of stories emphasizing that, when used in a way that is not approved, the drug provides little benefit to the patient's health. What should have been legitimate news about bad prescribing habits, became an illegitimate story about poor drug efficacy.

The new position from German authorities was based on ongoing review of a growing data set that demonstrates the drug's beneficial effects. This is reminiscent of the recent news from the UK where authorities changed their stance on the cost benefits of a group of Alzheimer's drugs, including Namenda, and began to cover the cost of their use.

There is no doubt that better treatments, be they drugs or other interventions, are needed in the Alzheimer's field. But the long debate about efficacy of the current drugs is being clarified through the ongoing collection of evidence that early intervention and proper treatment are beneficial.

We all know that emotionally intense experiences tend to be effectively stored for retrieval over a lifetime. This is an evolutionary mechanism that guides us away from dangerous situations we have previously encountered, and toward those where significant rewards were garnered. Since stress is correlated with emotional intensity, it makes sense that there is a relationship betwen stress and memory.

In a more thorough look at the relationship, researchers from the University of Edinburgh recently published their findings in the Journal of Neuroscience. According to their study, a moderate amount of stress can aid memory, but an intense or sustained amount of stress can be harmful.

They identified two distinct receptors in aging brains that react to cortisol, a hormone produced as a by-product of stress. The first receptor reacted to low levels of cortisol and improved memory. The other, which reacted to higher levels of cortisol, had a negative impact on memory capacity.

The most likely conclusion from this work is that a single stressful incindent is likely to be stored for later recall, but a lifestyle of sustained high stress, is likely to impair overall memory function.

With the announcement of new diagnostic guidelines, developed in tandem by the National Institute of Aging and the National Alzheimer's Association, we can now conceptualize the disease across a continuous spectrum with three contiguous stages of progression. There is a pre-clinical stage, a mild cognitive impairment stage, and a dementia stage.

Pre-clinical Stage
The purpose of defining this very early stage, before the presence of any clinical symptoms, is purely to benefit research. While there are no symptoms of disease in this stage, researchers have noted that certain biological changes, including protein levels in the brain, blood, and spinal fluid, seem to change in fairly predictable ways during the years before Alzheimer's patients manifest symptoms. The changes are not sufficiently telling to diagnose the disease at this early stage, but identifying these individuals and enlisting them as research subjects is an important goal for the field.

Importantly, physicians will not use these criteria to diagnose such early stage Alzheimer's. The definition of this stage is purely to help researchers speak a common language about similarly characterized research subjects.

Mild Cognitive Impairment Stage
In this stage, patients have clear underlying pathology consistent with Alzheimer's disease, and have also developed clinical symptoms of memory loss or other cognitive deficits.

The identification of this stage is the most important aspect of the new guidelines, as it will enable earlier intervention for patients who are, almost certainly, in the progressive throes of Alzheimer's, but still have relatively healthy brains. It is hoped that existing treatments, and new treatments in the pipeline, will be optimally effective in these early stage patents.

Dementia Stage
This stage is quite consistent with our former view of the disease. It requires the hallmark pathology of amyloid plaques in the brain, plus cognition so impaired as to meet the criteria for dementia (two or more realms of impaired cognition that interrupt daily activities of living). In the past, we did not call the problem "Alzheimer's disease" until the patient reached this end stage condition.

The announcement of new guidelines for diagnosing Alzheimer's disease is being widely covered in the press today. The move is a solid step in the right direction, but is spawning some confusion about why the change is necessary, and how it might help.

Biggest Change: AD starts prior to Dementia
The most important change is that we will now recognize Alzheimer's disease in its early stages, prior to the patient suffering massive brain damage and becoming demented. This is a more difficult diagnosis to make and, as such, requires a thoughtful approach.

Perspective on Former Guidelines
According to the former guidelines, put in place nearly 30 years ago, Alzheimer's disease was defined in part by the presence of dementia. As readers of this blog know, dementia requires impairment so severe that a person cannot independently care for themselves. In this regard, the term "mild Alzheimer's" means "barely demented due to Alzheimer's pathology"' This is a misnomer because, even in its "mild" stages, dementia is a severe condition.

To put that in perspective, imagine if we could note the high blood sugar and blurry vision caused by diabetes, but we couldn't diagnose and treat it until the patient's kidneys failed. Any guideline, suggesting that symptoms must be severe before diagnosis, is in direct conflict with early intervention.

The former guidelines were problematic as illustrated by this example: Suppose a 75 year old person, with a family history of Alzheimer's, noticed subtle signs of memory loss and visited a physician. The physician then confirmed the declining memory and sought the cause of the problem. After ruling out depression, sleep disorders, medications, thyroid malfunction, poorly controlled diabetes, vitamin deficiency, and stroke as possible causes, he noted on an MRI scan of the brain that the patient's hippocampus was shrinking. This would be a strong indication of Alzheimer's disease.

However, since the patient in this example had only subtle memory loss, not severe cognitive impairment meeting the criteria for dementia, the physician could not diagnose Alzheimer's and initiate treatment. According to the old guidelines, the physician would let the Alzheimer's pathology progress for months or years, until the patient suffered enough irreversible brain damage to become demented, and then they could diagnose Alzheimer's and initiate treatment. That clearly makes no sense.

New Guidelines
Under the new guidelines, if a patient has memory loss or other cognitive deficits, and common causes of such deficits are ruled out, and pathology is consistent with Alzheimer's, then we should recognize the condition as early stage Alzheimer's disease and begin treating it. This holds even if the patient's cognitive problem is subtle and does not meet the criteria for dementia.

Since earlier intervention bodes well for better treatment outcomes, this is a solid step in the right direction.

Reporting the news is a business. This is why stories with market appeal, even if they have little news value, or may even be misleading, sometimes get broad coverage. I am sure most editors sincerely want to present the most important stories and filter out the trivial items, but there is always a tendency to promote a compelling headline.

Over the last two days, you may have seen headlines that Namenda, one of the approved Alzheimer's drugs on the US market, does not work for patients with mild AD. These headlines are based on an article published in this week's online issue of the Archives of Neurology. In this study, researchers at the University of Southern California, performed no new research on the drug, but reviewed data from three other published studies, and concluded that Namenda is not beneficial for patients with mild AD.

I am not sure why this has been so broadly reported in the press, and I would like to emphasize two points:

1) Namenda is not approved for use in mild stage patients, only for moderate and severe stage patients. This study reached exactly the same conclusions as the FDA reached when they approved the claims for the drug. No news there.

2) Namenda has been shown to benefit early stage patients when combined with other approved Alzheimer's medications such as Aricept and Exelon. To craft an interesting headline based on only half the story is fairly disingenuous.

To be fair to the press, there may be value in reporting that many physicians prescribe Namenda for early stage Alzheimer's and, if prescribed alone (without one of the other drugs shown to boost efficacy), then the effects are probably minimal for most patients. In that case, a legitimate framing for the story would convey that the drug is not being used properly, as opposed to conveying that the drug is not effective.

I have no ties to the pharmaceutical industry and I don't wish to sell false hope to the public about drug efficacy against Alzheimer's disease. However, some people respond better than others to existing treatments, and every one deserves the opportunity to find out how treatment will affect them. It is a shame to discourage physicians and patients from seeking potentially beneficial therapy just so you can sell more press with an eye-grabbing headline.

There is a lot of recent press suggesting that a brain scan may be useful in predicting Alzheimer's disease.

The excitement has been generated by a new study showing that a good read on the size and shape of particular portions of the brain, can be useful in predicting which patients, among a group with subtle symptoms of memory loss, will develop Alzheimer's disease.

The journalists at MSNBC, provide a good example of how the concept of "predicting" is frequently misused in the press, when they are actually writing about "identifying". Almost invariably, the confusion between predicting and identifying Alzheimer's, is coupled with the misleading notion that subtle symptoms of memory loss sometimes "progress" to Alzheimer's.

I want to untangle these various notions, and offer a clear summary of what I think these journalists are trying to convey.

Mild Cognitive Impairment
When a person has mild symptoms of memory loss that are more severe than those we expect with normal aging, but not severe enough to qualify as dementia, we describe their condition as "mild cognitive impairment" (MCI). By definition, MCI is not a part of normal aging. This means that it is caused by some underlying medical condition such as vascular disease, a thyroid disorder, depression or a number of other causes. It might also be due to early stage Alzheimer's disease.

Predicting vs. Identifying
The key point is, if you have MCI due to Alzheimer's disease, then you have Alzheimer's disease. There is no need to predict, only to identify. There is no concept of "progression", the disease is already present.

So, the recent study that has generated much press, is a good study with a potentially valuable conclusion. When a person has mild cognitive symptoms that we call MCI, and a physician must diagnose the correct cause of the symptoms in order to administer appropriate treatment, the ability to identify Alzheimer's disease as the cause (or not the cause), is very important. If a scan of brain structure is valuable in this regard, then we have gotten better at diagnosing this terrible disease.

We have not, however, found a new way to predict anything. Only a new way to better identify a disease that is already present.

This is definitely big news. But how do you define "big" as it pertains to news?

If you base your opinion on the amount of press coverage devoted to a story, and the prominence of the media outlets covering it, then the recent announcement that researcehrs have discovered 5 new genes associated with Alzheimer's disease is, indeed, "big" news.

However, it is not always clear why a story is big or important, and this often leads to misinterpretations about what a story might mean. With regard to the 5 new genes, I think the importance lies in the fact that, every new piece of explanatory data can help us understand Alzheimer's disease.

If you read the story and thought it meant that now we can tell who will get AD, you probably read too much into the discovery. If you thought it meant that we now know how to treat AD, you definitely read too much into the disovery.

AD is a very complex and poorly understood disease. Scientists have not yet isolated its cause, nor have they clearly mapped the progression of the multiple biological processes that unfold as the disease advances. There are some consistent elements, like an accumulation of beta-amyloid protein in the brain, and a falling ratio of amyloid/tau proteins in the blood and spinal fluid. We also generally see shrinkage of certain parts of the brain relative to others, and cognitive decline that usually begins with deficits in short-term memory.

But where it all begins, and which conditions lead to the next, is not clear. There may be important metabolic processes, chemical changes, immune responses, and inflammatory mechanisms that all play roles in how Alzheimer's progresses. Finding 5 new genes, with significant correlations to this disease, opens the door to better understanding which of these processes are most likely playing important roles.

To be clear, the better understanding we hope for, will require further work. The thought is that we can figure out what these 5 genes do, and that will tell us which processes might be most important to study as a means of understanding AD. As you can imagine, that might be a long road.

I think it is great that we have gained new clarity about the possible genetic underpinnings of Alzheimer's disease. But this is a big news story because it will help us focus future research toward a better understanding of the disease, not because we have unlocked any immediate secrets for better diagnoses or treatments.